Total synthesis of GEX1Q1, assignment of C-5 stereoconfiguration and evaluation of spliceosome inhibitory activity

Abstract

An enantioselective total synthesis of GEX1Q1 has been accomplished in a convergent manner. The C-5 asymmetric center has now been assigned through synthesis. GEX1Q1 displayed slightly better spliceosome inhibitory activity over its C-5 epimer. The salient features of this synthesis include an asymmetric hetero-Diels-Alder reaction to construct the tetrahydropyran ring and a Suzuki cross-coupling to assemble the key segments. © 2014 American Chemical Society.